Kalirin inhibition of inducible nitric-oxide synthase

Nitric oxide (NO) acts as a neurotransmitter. However, excess NO produced from neuronal NO synthase (nNOS) or inducible NOS (iNOS) during inflammation of the central nervous system can be neurotoxic, disrupting neurotransmitter and hormone production and killing neurons. A screen of a hippocampal cDNA library showed that a unique region of the iNOS protein interacts with Kalirin, previously identified as an interactor with a secretory granule peptide biosynthetic enzyme. Kalirin associates with iNOS in vitro and in vivo and inhibits iNOS activity by preventing the formation of iNOS homodimers. Expression of exogenous Kalirin in pituitary cells dramatically reduces iNOS inhibition of ACTH secretion. Thus Kalirin may play a neuroprotective role during inflammation of the central nervous system by inhibiting iNOS activity.     

Genitourinary anomalies in the CHARGE association

PURPOSE: We identified the incidence and types of genital and urinary anomalies, and established a plan for evaluating the urinary system in the CHARGE association. MATERIALS AND METHODS: We retrospectively reviewed the charts of 32 patients in whom the CHARGE association was diagnosed. RESULTS: Of the 32 patients identified 22 (69%) had genitourinary abnormalities. Genital anomalies, including micropenis, penile agenesis, hypospadias, chordee, cryptorchidism, a bifid scrotum, atresia of the uterus, cervix and vagina, and hypoplastic labia majora, labia minora and clitoris, were present in 18 patients (56%). Of the 24 patients who underwent renal ultrasound 10 (42%) were diagnosed with urinary tract anomalies including a solitary kidney, hydronephrosis, renal hypoplasia and duplex kidneys. Further evaluation revealed vesicoureteral reflux, neurogenic bladder secondary to spinal dysraphism, nephrolithiasis, ureteropelvic junction obstruction and a nonfunctioning upper pole in both duplex kidneys. CONCLUSIONS: There is a high incidence of genitourinary anomalies in the CHARGE association. Because of this high incidence of anomalies, patients with this condition should undergo a careful genitourinary evaluation, including renal and bladder ultrasound, and voiding cystourethrography screening.     

Edible mushroom (Agaricus bisporus) lectin, which reversibly inhibits epithelial cell proliferation, blocks nuclear localization sequence-dependent nuclear protein import

The Galbeta1-3GalNAcalpha (TF antigen)-binding lectin (ABL) from the common edible mushroom (Agaricus bisporus) has a potent anti-proliferative effect without any apparent cytotoxicity. This unusual combination of properties prompted investigation of its mechanism of action. In contrast to soluble lectin, agarose-immobilized, and hence noninternalizable ABL had no effect on proliferation of HT29 colon cancer cells. Electron microscopy of HT29 cells incubated with fluorescein- and gold-conjugated ABL showed internalization of the lectin into endocytotic vesicles and multivesicular bodies. Confocal microscopy showed perinuclear accumulation of fluorescein isothiocyanate-conjugated lectin, which also inhibits HT29 cell proliferation, raising the possibility that the lectin might interfere with nuclear pore function. Transport of heat shock protein 70 into the nucleus in response to heat shock was blocked by preincubation of HT29 cells for 6 h with 40 micrograms/ml ABL. In digitonin-permeabilized cells, nuclear uptake of bovine albumin conjugated to a nuclear localization sequence (NLS)-containing peptide was also inhibited by a 15-min preincubation with 40-100 micrograms/ml ABL. In contrast, serum-stimulated nuclear translocation of mitogen-activated protein kinase, which is NLS-independent, was not affected by pretreatment of cells with the lectin. These results suggest that the anti-proliferative effect of ABL is likely to be a consequence of the lectin trafficking to the nuclear periphery, where it blocks NLS-dependent protein uptake into the nucleus.     

Metabolic transformations of leukotriene B4 in primary cultures of human hepatocytes

Analytic expressions for plasma total titratable base, base excess (DeltaCB), strong-ion difference, change in strong-ion difference (DeltaSID), change in Van Slyke standard bicarbonate (DeltaVSSB), anion gap, and change in anion gap are derived as a function of pH, total buffer ion concentration, and conditional molar equilibrium constants. The behavior of these various parameters under respiratory and metabolic acid-base disturbances for constant and variable buffer ion concentrations is considered. For constant noncarbonate buffer concentrations, DeltaSID = DeltaCB = DeltaVSSB, whereas these equalities no longer hold under changes in noncarbonate buffer concentration. The equivalence is restored if the reference state is changed to include the new buffer concentrations.     

Reference data sets for vertical borehole ground heat exchanger models and thermal response test analysis

Ground source heat pump systems often use vertical boreholes to exchange heat with the ground. Two areas of active research are the development of models to predict the thermal performance of vertical boreholes and improved procedures for analysis of in situ thermal conductivity tests, commonly known as thermal response tests (TRT). Both the models and analysis procedures ultimately need to be validated by comparing them to actual borehole data sets. This paper describes reference data sets for researchers to test their borehole models. The data sets are from a large laboratory “sandbox” containing a borehole with a U-tube. The tests are made under more controlled conditions than can be obtained in field tests. Thermal response tests on the borehole include temperature measurements on the borehole wall and within the surrounding soil, which are not usually available in field tests. The test data provide independent values of soil thermal conductivity and borehole thermal resistance for verifying borehole models and TRT analysis procedures. As an illustration, several borehole models are compared with one of the thermal response tests.     

New interdigital design for large area dye solar modules using a lead‐free glass frit sealing

A new interdigital design for large area dye solar modules is developed for an area of 30×30 cm². This design requires fewer holes in the glass substrate for electrolyte filling, than the conventional strip design. A complete manufacturing process of this module—ranging from screen printed layers to semi‐automated colouring and electrolyte filling—in a laboratory‐scale baseline is illustrated. As primary sealing method, a durable glass frit sealing is used. It is shown, that the lead (Pb) content present in many glass frit powders contaminates the catalytic platinum electrode during the sintering process, resulting in a lowering of the fill factor. A screen printable lead‐free glass frit paste is developed, which solves this problem. Long term stability tests are presented on 2·5 cm² dye solar cells, which have been completely sealed with glass frit. In consecutively performed accelerated ageing tests under 85°C in the dark (about 1400 h) and continuous illumination with visible light (1 sun, about 1700 h), a 2·5 cm² dye solar cell with an electrolyte based on propylmethylimidazolium iodide showed an overall degradation of less than 5% in conversion efficiency. In a subsequently performed thermal cycling test (−40°C to +85°C, 50 cycles) a 2·5 cm² dye solar cell with the same electrolyte composition also showed only a slight degradation of less than 5% in conversion efficiency. Copyright © 2006 John Wiley & Sons, Ltd.     

The C-terminal domains of gammaS-crystallin pair about a distorted twofold axis

The 2-domain gammaS-crystallin, a highly conserved early evolutionary off-shoot of the gamma-crystallin family, is located in the water-rich region of eye lenses. The expressed C-terminal domain, gammaS-C, has been crystallized and the 2.56 A X-ray structure determined. There are two domains in the asymmetric unit which pair about a distorted twofold axis. One of the domains has an altered conformation in a highly conserved region of the protein, the tyrosine corner. The distorted gammaS-C dimer of domains is compared with the highly symmetrical, equivalent recombinant dimer of C-terminal domains from gammaB- crystallin. Sequence changes close to the interface, that distinguish gammaS from the other gamma-crystallins, are examined in order to evaluate their role in symmetrical domain pairing.